1 Neurology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.3 Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.4 University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.5 Virginia Commonwealth University School of Medicine, Richmond, Virginia, United States of America.6 School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.7 School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.8 University of Nebraska Medical Center, Omaha, Nebraska, United States of America.9 Stanford University School of Medicine, Stanford, California and VA Health Care System, Palo Alto, California, United States of America.10 School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, Nebraska, United States of America.11 Neurology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU

DOI:

10.1371/journal.pone.0098506

Abstract:

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139-151 and myelin basic protein 89-101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139-151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139-151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, and they can transfer disease to naïve animals. Likewise, the animals first primed with suboptimal dose of PLP 139-151 and later infected with ACA, developed EAE, suggesting that ACA infection can trigger CNS autoimmunity in the presence of preexisting repertoire of autoreactive T cells. Taken together, the data provide novel insights into the pathogenesis of Acanthamoeba infections, and the potential role of infectious agents with mimicry epitopes to self-antigens in the pathogenesis of CNS diseases such as multiple sclerosis.